1. Field of the Invention
The present invention relates to novel chiral ligands derived from new spiro compounds and their utilities in catalysts for applications in asymmetric catalysis. More particularly, the present invention relates to metal complexes of these chiral spiro ligands. The metal complexes according to the present invention are useful as catalysts in asymmetric reactions, such as hydrogenation, hydride transfer, allylic alkylation, alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, olefin metathesis, hydrocarboxylation, Epoxidation, isomerization, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition; Mannich reaction, epoxidation, kinetic resolution, [m+n] cycloaddition and chiral Lewis acid catalyzed reactions.
2. Description of Related Art
Discovery of new chiral ligands sets the foundation of highly enantioselective transition metal-catalyzed reactions. Many chiral ligands have been developed for asymmetric catalysis, however, only few chiral ligands or motifs are suitable for the synthesis of chiral molecules in industry and academic lab. Transition-metal catalyzed enantioselective hydrogenation is a powerful strategy to synthesize chiral substances from unsaturated starting materials. Since DIOP ligand was discovered by Kagan in 1971 (Kagan, H. B.; Dang, T.-P. Chem. Commun. 1971, 481. (b) Kagan, H. B.; Dang, T.-P. J. Am. Chem. Soc. 1972, 94, 6429), a large number of bidentate ligands, especially those diphosphine ligands with C2-symmetry, have been developed for highly efficient asymmetric hydrogenation of various olefins, ketones, and imines. In comparison, monodentate ligands had been much less successful due to due to the conformational flexibility of their metal/ligand complexes. However, recent advances, indicated that monodentate ligands can be effective for asymmetric hydrogenation. For example, MonoPhos has been prepared from BINOL) (Claver, C.; Fernandez, E.; Gillon, A.; Heslop, K.; Hyett, D. J.; Martorell, A.; Orpen, A. G.; Pringle, P. G. Chem. Commun. 2000, 961. Reetz, M. T.; Mehler, G. Angew. Chem., Int. Ed. Engl. 2000, 39, 3889, Hua, Z.; Vassar, V. C.; Ojima, I. Org. Lett. 2003, 5, 3831, Hulst, R.; de Vries, K.; Feringa, B. L. Tetrahedron: Asymmetry 1994, 5, 699. Berg, M. v. d.; Minnaard, A. J.; Schudde, E. P.; Esch, J. v.; Vries, A. H. M. d.; Vries, J. G. d.; Feringa, B. L. J. Am. Chem. Soc. 2000, 122, 11539. Pen, D.; Minnaard, A. J.; Vries, J. G. d.; Feringa, B. L. J. Am. Chem. Soc. 2002, 124, 14552). Excellent enantioselectivities in Rh-catalyzed asymmetric hydrogenation of α-, β-dehydroamino acid derivatives, itaconic acid derivatives, and enamides. Using 1,1-spirobiindane-7,7-diol (Birman, V. B.; Rheingold, A. L.; Lam, K.-C. Tetrahedron: Asymmetry 1999, 10, 125), Zhou et. al. have prepared a series of spiro monodentate phosphoramidite ligands (SIPHOS), and good to excellent results (Fu, Y.; Xie, J.-H.; Hu, A.-G.; Zhou, H.; Wang, L.-X.; Zhou, Q.-L. Chem. Commun. 2002, 480. Hu, A.-G.; Fu, Y.; Xie, J.-H.; Zhou, H.; Wang, L.-X.; Zhou, Q.-L. Angew. Chem. Int. Ed. 2002, 41, 2348. Zhu, S.-F.; Fu, Y.; Xie, J.-H.; Liu, B.; Xing, L.; Zhou, Q.-L. Tetrahedron: Asymmetry 2003, 14, 3219. Fu, Y.; Guo, X.-X.; Zhu, S.-F.; Hu, A.-G.; Xie, J.-H.; Zhou, Q.-L. J. Org. Chem. 2004, 69, 4648) have been achieved in asymmetric hydrogenation reactions (FIG. 1). Despite this success, the method for making this spirodiol is too long and tedious and the application of these ligands and catalysts are limited.

In searching for new structural motifs, we found that 9,9′-spirobixanthene was first synthesized in the 1930s (Clarkson, R. G.; Gomberg, M. J. Am. Chem. Soc. 1930, 52, 2881), and no further attempts had been made to assemble functional groups onto its aromatic rings. We therefore modified this spirocyclic framework into a new C2-symmetrical 9,9′-spirobixanthene-1,1′-diol (FIG. 2), which possesses larger biting angle and more rigid coordinating structure than BINOL. This new spirocyclic diol (A) is among the most accessible (in one case with only two-step synthesis) diols reported to date and can be made practically for many applications.

To demonstrate its potential role in asymmetric catalysis, spiro monodentate phosphoramidite ligand (B) (FIG. 2) was prepared, which exhibited excellent enantioselectivity (up to 99% ee) in Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid derivatives and itaconic acid.